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(1) CYTOTOXIC DRUGS

DRUG MOA
Bifunctional alkylation

CLINICAL USE
Nitrogen Mustard MOPP regimen for HODGKINS LYMPHOMA Phosphoramide Mustard Sarcomas Prior to Bone Marrow transplantation Chronic B-cell lymphocytic leukemia and lymphoma Immunosuppressive therapy (SLE/ Rheumatoid therapy) Prior to Bone Marrow transplantation Gliomas; Brain tumors Multiple myeloma Bone marrow transplant ABVD regimen for HODGKINS LYMPHOMA Gliomas Radiation therapy

TOXICITY
Tissue necrosis

ANTIDOTE

ALKYLATING AGENTS
Mechlorethamine Cyclophosphamide Ifosfamide Melphalan Chlorambucil
Monofunctional alkylation

Hemorrhagic cystitis Hemorrhagic cystitis Mesna

Busulfan Nitrosoureas
Penetrates the CSF Carmustine / BCNU

Venoocclusive disease of the liver Phenobarbital

Dacarbazine Temozolomide

Generates active metabolite: MTIC (Monomethyl triazenoimidazole carboxamide) Dacarbazine analog

Flu-like syndrome of fever malaise, myalgias

Acetaminophen predication

ANTIMETABOLITES
(1) FOLIC ACID ANALOGS Methotrexate
Inhibits DHFR enzyme (DIHYDROFOLATE REDUCTASE) S-phase specific Unable to polyglutamate methotrexate

Intrathecal prophylaxis in

lymphomas & leukemias Choriocarcinoma NON-HODGKINS LYMPHOMA Osteosarcoma Leukemia Urine alkalinization 1 line metastatic mesethelioma nd 2 line metastatic nonsmall cell lung cancer
st

Accumulation in 3 spaces (Ascites, Pleural effusion) Bone marrow suppression

rd

Leucovorin

Permetrexed

Multifolate antagonist Inhibits tumor enzymes

Vitamin B and Folic acid

(2) PYRIMIDINE ANALOGS


5-FU
Inhibits Thymidilate Synthase Inactivated by Dihydropyrimidine Dehydrogenase enzyme in the liver Colorectal cancer Breast cancer Leucovorin

Capecitabine
(prodrug of 5-FU)

---Converted by Thymidine Phosphorylase to 5-FU Analog of 2-deoxycytidine Converted by Deoxycytidine kinase to an active for of 5 Induction of remission to ALL

Hand-foot syndrome

Cytarabine

Myelosuppression GI disturbances Conjunctivitis

Gemcitabine

monophosphate nucleotide --- Only drug effective for pancreatic cancer Mild therapy; no alopecia Myelosuppresion

(3) PURINE ANALOGS inhibits HGPRT enzymes Guanine analog Mercaptopurine Thioguanine Fludarabine Cladribine
Guanine analog

Induction of remission to ALL Induction of remission to AML Chronic lymphocytic leukemia Hairy cell leukemia

Myelosuppression Myelosuppression

Adenosine analog

CD4 T-cells depletion CD4-Tcells depletion

Adenosine analog

ANTIMITOTIC
(1) VINCA ALKALOIDS
Vincristine
NON-HODGKINS LYMPHOMA together with CHOP (Cyclo, Prednisone, Doxorubicin) HODKINS LYMPHOMA together with MOPP (Meclorethamine, Prednisone, Procarbazine) HODGKINS LYMPHOMA together with ABVD (Doxorubicin, dacarbazine, bleomycin) Adjuvant and metastatic NSCLCA Neurotoxicity, numbness, tingling, loss of DTR

M-phase specific; Binds to tubulin causing microtubule dissollution

Myelosuppression

Vinblastine

Vinorelbine

Myelosuppression

(2) TAXANE Paclitaxel


Promotes, rather than inhibits microtubule formation Prevents microtubule destabilization
Breast cancer Lung cancer Ovarian cancer Neutropenia Neuropathy More pronounced neutropenia than paclitaxel Metabolized in the liver by CYT p450 Metastatic Breast cancer Cromophore vehicle

Docetaxel (3) EPOTHILONES Ixabepilone

Similar to taxanesbut MORE POTENT!

Metabolized in the liver by CYT p450

TOPOISOMERASE- INTERACTIVE AGENTS


(1) CAMPHOTERICIN Irinotecan
Major excretion pathway is GLUCORONIDATION by UGT1A1 s Patients with CRIGGLER NAJAR/ GILBERTS SYNDROME are more affected Delayed & Acute diarrhea

Metastatic ovarian cancer TOPOTECAN

Neutropenia

(2) EPIPODOPHYLLOTOXINS
Etoposide
Conditions lowering albumin levels will lead to increased free fraction, increasing toxicities Acute nonlymphocytic leukemia

TUMOR ANTIBIOTICS
(1) ANTHRACYCLINES Doxorubicin Daunorubicin Epirubicin Mitoxantrone Liposomal doxorubicin (2) BLEOMYCIN
Oxidative DNA damage Binds with Topoisomerase-II Generates free radicals Intercalates DNA Promotes apoptosis Lymphomas, Leukemia, Breast cancer, Sarcoma, SCLCA ALL and AML Breast Cancer Acute non-lymphocytic leukemia, hormone-resistant prostate cancer Ovarian cancer Lymphomas Less cardiotoxic Cardiotoxicity due to free radicals generated

Tumor antibiotic from streptococcus spp.

(3) MITOMYCIN

ANAL CANCER!

Less cardiotoxic, less neutropenia Pulmonary fibrosis Decline in CO2 diffusion capacity Cutaneous toxicity HUS

PLATINUM COMPOUNDS forms DNA ADDUCTS which are recognized by MMR, that will promote apoptosis
Cisplatin
ALL Germ cell tumor Lung cancer Head and neck cancer Ovarian cancer Ovarian cancer Lung cancer GI cancer, Ovarian cancer Germ cell cancer Cervical cancer Pancreatic cancer Nephrotoxicity Most emetogenic Renal toxicity Ototoxicity Myelosuppression

Carboplatin Oxaliplatin

Less reactive than cisplatin, better tolerated Less neutropenia Less nephrotoxic, more neuropathic Hypersenistivity reactions Mimimal Bone marrow and GI toxicity Hyperglycemia, Hypoalbuminemia, protein C and S deficiency Adrenocortical carcinoma

L-asparaginase

Mitotane

(2) HORMONAL TREATMENT


DRUG

Adrenocorticosteroids

MOA Promote apoptosis

Aromatase Inhibitors

Prevent formation of estrogen from adrenal gland and adipose tissue by inhibiting AROMATASE

CLINICAL USE Immunosuppresion Glucose intolerance Osteoporosis Water retention GI ulcers Bone mineral density, bone pains, increased fracture rates Musculoskeletal problems!

TOXICITY

Anti-Estrogen

For post-menopausal ER/PR+ breast cancer patients in adjuvant, neoadjuvant, metastatic setting Blocks estrogen receptors itself

GnRH analogs

Stimulates FSH and LH production by the pituitary gland then will late cause negative feedback inhibition Binds to androgen receptors and causes complete androgen blockade

Breast cancer Prostate cancer

Thrombosis risk Endometrial CA Hot flashes, nausea, vomiting, menstrual irregularities Initial flare reaction

Anti-androgen

Prostate cancer

Decreased libido Hot flashes Gynecomastia Mastodynia Paradoxical stimulation of androgen receptors

BIOLOGICAL RESPONSE MODIFIERS


DRUG

Interleukin-2

CLINICAL USE Expands T-cell response that is cytolytic for tumor cells Melanoma Renal cell carcinoma AML Filgrastim/ Lenograstim Expands population of neutrophil precursors Prophylaxis for chemotherapy induced neutropenia

SIDE EFFECT Hypotension Peripheral edema Azotemia

ANTIDOTE

G-CSF

Fever Chills

TARGETED RESPONSE
DRUG CLINICAL USE Her2 receptor Vegf receptor Breast cancer Angiogenesis SIDE EFFECT CHF Hypersensitivity ANTIDOTE

MONOCLONAL ANTIBODIES
Traztuzimab Bevacizumab Cetuximab Panitumomab Rituximab Imatinib (Gleevec) Gefitinib Erlotinib Sunitinib Sorafenib
Hypertension, bleeding, proteinuria Hypersensitivity reactions Skin rashes Hypersensitivity reactions Hypersensitivity reactions Hypersensitivity reactions

EGFR receptor

EGFR receptor CD20 receptor

Colorectal cancer Head and neck cancer Colorectal cancer B-cell lymphomas

TYROSINE KINASE INHIBITORS


Bcr-Abl TKO in CML CD 117 TKl in GIST EGFR TKl in NSCLCA EGFR TKl in NSCLCA Multikinase Renal and liver cancer Multikinase Renal and liver cancer

Rashes Asthenia Weakness

Lapatinib

EGFR and HER2 TKl Breast Head and neck cancer

PROTEOSOME INHIBITOR
Bortezomib
Degrades proteosomes that denatures IKb Pancreatic neuroendocrine tumors Advanced renal cell cancer Advanced renal cell cancer

MTOR INHIBITOR
Everolimus Temsirolimus
Intrathecal Administration Can cross Blood Brain Barrier

Methotrexate Cytarabine Nitrosoureas Temoxolomide Teniposide Hydroxyurea

Cytotoxic agent (Antimetabolite) Cytotoxic agent (Antimetabolite) Cytotoxic agent (Alkylating agent) Cytotoxic agent (Alkylating agent) Topoisomerase interactive agent